Rapamycin and autoimmunity

#1

There is a strong association between obesity and autoimmune diseases.

The link between obesity and autoimmunity

Overnutrition could lead to loss of self-tolerance by impinging on immune regulation
https://www.science.org/doi/10.1126/science.ade0113

Of interest to us is the link between increased circulating levels of nutrients and overactive mTOR in T cells.
This overactive state leads to inhibition of the expression of regulatory T cells, also known as Tregs,which are important suppressor agents of autoimmunity.
By inhibiting TOR, rapamycin can prevent autoimmunity by increasing the activity of Tregs.

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#2

Thank you for bringing up MTOR and autoimmunity. T-cell dysfunction in SLE patients might be targeted by NAC and inhibition of mTOR (by NAC).

N-ACETYLCYSTEINE REDUCES DISEASE ACTIVITY BY BLOCKING MTOR IN T CELLS OF LUPUS PATIENTS - PMC (nih.gov)

"Systemic lupus erythematosus (SLE) patients exhibit T-cell dysfunction which can be regulated through the mitochondrial transmembrane potential (Δψm) and mammalian target of rapamycin (mTOR) by glutathione. Therefore, the safety, tolerance, and efficacy of glutathione-precursor N-acetylcysteine (NAC) were examined in this randomized double-blind placebo-controlled study…

…NAC increased Δψm (p=0.0001) in all T cells, it profoundly reduced mTOR activity (p=0.0001), enhanced apoptosis (p=0.0004) and reversed expansion of CD4−/CD8− T cells (1.35 ± 0.12-fold; p=0.008), stimulated Foxp3 expression in CD4+/CD25+ T cells (p=0.045), and reduced anti-DNA production (p=0.049)."

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#3

Table 1 is a shortcut to some relevant papers regarding rheumatic diseases and mTOR. .

#4

Very nice and comprehensive article Curious.

I think the role of rapamycin in expanding the Treg population of T cells is very important in regulating autoimmunity. I’m very impressed by several studies suggesting a role for rapamycin in both preventing and treating MS since it may help to replete the myelin sheath.

One note of concern is that TOR2 is involved in the production of autoantibodies, but we’re concerned about inhibiting it to any significant degree. It’s all very complicated.

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